Multimodality Microendoscope for Metastatic Ovarian Cancer Detection & Treatment

描述（由申请人提供）：卵巢上皮癌是美国女性癌症死亡的第五大原因，在所有妇科癌症中病死率最高。卵巢癌特别危险，因为它有迅速转移的倾向，因为这种疾病通过从原始肿瘤脱落侵入整个腹部的组织。90%的卵巢癌死亡都是由这种隐性转移性疾病引起的，这种疾病通常由大量的微转移组成，很难被发现。虽然白光和荧光内窥镜已经被使用，但它们的选择性和灵敏度太有限，无法准确检测显微镜下致命的转移瘤，而没有高假阳性和假阴性率。由于没有能力检测这种亚临床疾病状态，许多妇女错过了替代化疗或放射治疗可能挽救生命的关键时期。该项目的长期目标是通过建立、测试和部署一种灵敏的微转移检测新范式来提高卵巢癌的低生存率（<30%）。在第一个目标中，本建议将荧光原位显示可疑肿瘤与结构敏感的光学相干断层扫描（OCT）成像技术相结合，为卵巢癌诊断提供选择性、敏感性和全定量的显微成像探针。通过利用荧光检测快速检查和OCT三维结构成像，这种原位探针不仅可以可视化肿瘤，还可以呈现其潜在的组织结构，大小和血管系统。这种方法将被实现为一个由成千上万个单独的图像元素组成的显微内窥镜，这些图像元素被近端扫描，以确保小的远端形状因素，以实现微创成像。在第二个具体目标中，三维肿瘤模型和离体组织将用于广泛的表征和编目，以便多模态对比可用于任何组织中隐匿转移性疾病的原位诊断。这些实验将立即用于第三个目标，在该目标中，显微内窥镜将用于原位评估两种治疗方案下弥散性卵巢癌小鼠模型的微转移治疗效果。一项实验将研究化疗药物阿霉素的有效性，而第二种方法将使用光动力疗法，其中使用光敏剂产生细胞毒性物质以破坏肿瘤。

DESCRIPTION (provided by applicant): Ovarian epithelial cancer is the fifth leading cause of cancer death among women in the US, and has the highest fatality-to-case ratio of all gynecological cancers. Ovarian cancer is especially dangerous due to its propensity to rapidly metastasize, as the disease invades tissues throughout the abdomen by exfoliating from the original tumor. 90% of all ovarian cancer fatalities arise from this occult metastatic disease, which often is composed of a multitude of micrometastases that are exceedingly difficult to detect. While white-light and fluorescence endoscopy have been used, their selectivity and sensitivity have been too limited to accurately detect the microscopic, deadly metastases without high false-positive and false-negative rates. Without the ability to detect this sub-clinical disease state, many women miss a critical period where alternative chemotherapy or radiation treatment might be lifesaving. It is the long-term goal of this project to improve the dismal survival rates (<30%) of ovarian cancer by building, testing, and deploying a sensitive new paradigm for micrometastases detection. In the first aim, this proposal combines the visualization of suspect tumors in situ by fluorescence with the structurally sensitive optical coherence tomography (OCT) imaging technology to provide a selective, sensitive, and fully quantitative microscopic imaging probe for ovarian cancer diagnostics. By utilizing the fluorescence detection for rapid examination and OCT for 3D structural imaging, this in situ probe will not only visualize a tumor, but also render its underlying tissue structure, size, and vasculature. This approach will be realized as a microendoscope composed of tens of thousands of individual image elements that are scanned proximally to ensure a small distal form factor for minimally invasive imaging. In the second specific aim, three-dimensional tumor models and ex vivo tissues will be used for extensive characterization and cataloging so that the multimodal contrast can be used for in situ diagnosis of occult metastatic disease in any tissue. These experiments will find immediate use in the third aim, where the microendoscope will be used in situ to assess micrometastases treatment effectiveness in a mouse model of disseminated ovarian cancer for two treatment regimens. One experiment will study the effectiveness of the chemotherapy Adriamycin, while a second approach will use photodynamic therapy, where photosensitizers are used to generate cytotoxic species for tumor destruction. PUBLIC HEALTH RELEVANCE: This project proposes the construction of a new microscopic fiber probe for the selective detection of deadly ovarian cancer metastatic tumors. By detecting these metastases, this research aims to vastly improve the detection and subsequent treatment of ovarian cancer to save the lives of women with this disease.